Caprine arthritis-encephalitis virus (CAEV) is a non-oncogenic, exogenous retrovirus which causes a persistent infection of the reticuloendothelial system of goats. Clinical disease is a demyelinating encephalitis in young goats and a progressive arthritis in adults which experience periodic relapses of acute lameness. Lesions in the nervous system and joints are characterized by mononuclear infiltrates. We plan to examine the pathogenesis of early inflammatory lesions in the nervous system joints and the response of the immune system to persistent virus infection over time. Immunosuppression of animals prior to virus inoculation inhibits the inflammatory response suggesting lesions are immune-mediated. We propose to examine cells from blood, cerebrospinal fluid (CSF), and synovial fluid for cytotoxicity by chromium release assay. Humoral and cellular immunity to CAEV will be measured by ELISA and lymphocyte stimulation respectively to determine if there is a cyclic response. In addition, CSF will be examined for heterologous viral antibody as seen with multiple sclerosis patients to determine if persistent infection of the nervous system causes recruitment and amplification of committed B cell clones. Animals will be monitored for fluctuating viremia. The temporal relationship of increased numbers of infected mononuclear cells to the immune responses and apparent clinical exacerbations will be recorded. Finally, we will examine sequential viral isolates from persistently infected goats for evidence of genetic variation.